The genetic determinants of human lysosomal enzymes will be analyzed in human-rodent somatic cell hybrids. Electrophoretic systems capable of separating isozymes containing a human subunit from rodent isozymes will be developed, along with histochemical stains capable of demonstrating the various lysosomal enzymic activities in the electrophoretic patterns. These techniques will be applied to the somatic cell hybrids to assign the genetic determinants of the lysosomal enzymes to specific human chromosomes. This approach will be used to assess both the determinants of enzyme structure (structural genes) and any genetic factors which modify or regulate the expression of the structural genes. In addition, heterokaryon formation will be used to assess complementation between cells from patients with clinical variants of selected lysosomal enzyme deficiencies.